Combining therapeutic vaccines with chemo- and immunotherapies in the treatment of cancer

ABSTRACT

Introduction

Breakthroughs in cancer immunotherapy have spurred interest in the development of vaccines to mediate prophylactic protection and therapeutic efficacy against primary tumors or to prevent relapse. However, immunosuppressive mechanisms employed by cancer cells to generate effective resistance have hampered clinical translation of therapeutic cancer vaccines. To enhance vaccine efficacy, the immunomodulatory properties of cytoreductive therapies could amplify a cancer-specific immune response.

Areas covered

Herein, the authors discuss therapeutic cancer vaccines that harness whole cells and antigen-targeted vaccines. First, recent advancements in both autologous and allogeneic whole-cell vaccines and combinations with checkpoint blockade and chemotherapy are reviewed. Next, tumor antigen-targeted vaccines using peptide-based vaccines and DNA-vaccines are discussed. Finally, combination therapies using antigen-targeted vaccines are reviewed.

Expert opinion

A deeper understanding of the immunostimulatory properties of cytoreductive therapies has supported their utility in combination therapies involving cancer vaccines as a potential strategy to induce a durable anti-tumor immune response for multiple types of cancers. Based on current evidence, combination therapies may have synergies that depend on the identity of the cytotoxic agent, vaccine target, dosing schedule, and cancer type. Together, these observations suggest that combining cancer vaccines with immunomodulatory cytoreductive therapy is a promising strategy for cancer therapy.

KEYWORDS:

• Cancer vaccine
• chemotherapy
• immunotherapy
• drug delivery

Article highlights

• Whole cell-based vaccines, whether autologous or allogenic, preclude identification of specific tumor associated antigens. However, their manufacturing process is labor-intensive and has limited scalability.

• Cancer-antigen specific cancer vaccines rely on the expression of cancer antigens by patient tumors.

• In many clinical trials, therapeutic cancer vaccines elicited a robust T cell response but were unable to mediate sustained tumor regression.

• Combining cancer vaccines with chemotherapy or immune checkpoint blockade can enhance the anti-tumoral effect of the cancer vaccine and improve outcomes.

• The combination of cancer vaccines with chemotherapy or immune checkpoint blockade represent the most probable path towards clinical translation of therapeutic cancer vaccines.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are funded by the American Cancer Society [via grant number IRG-15-172-45-IRG] and the National Institutes of Health [via a National Cancer Institute grant T32 CA153915 and a National Institute of Arthritis and Musculoskeletal and Skin Diseases grant T32 AR064194].